The overall objective of the project is to analyze the mechanism of the transformation of the previously studied changes in the protein and enzyme pattern of cross-reinnervated muscle and of muscles stimulated through the intact nerve with an activity pattern corresponding to the opposite type, and to determine the influence of the ontogenic stage of the muscle upon the change. One of the important questions in this area is whether slow muscle can be transformed to fast by the imposition of bursts of high frequency pulse trains. An anesthetic cuff will be utilized to suppress normal slow nerve activity. Stimulation will be carried out with a wireless transmitter and implanted reciever. This equipment permits variation of the parameters of the stimulus pattern both in an acute and chronic fashion. In addressing the question of the participation of trophic substances elaborated by the nerve attempts will be made to carry out transformation by imposing an alien type pattern following denervation. In parallel with studies on changes in the protein and enzyme pattern the distribution of mRNA coding for various protein types will be investigated to determine whether the protein changes are the result of the production of mRNA's previously not present or whether translational control in pre-existing mRNA's is involved. In vivo studies will be supplemented by the electrical stimulation of muscle cultures where, according to preliminary results, protein subunits corresponding to the stimulus pattern are formed. This system is well suited to study transformation not involving neural activity and will also permit the analysis of the transcription/translation events accompanying transformation. The response of the organism in different stages of ontogenetic development to imposed stimulus patterns will be examined utilizing post-partum and aged animals. The significance of these studies lies both in their explicatory value for certain adaptive regeneration processes in muscle and in the light they may shed on the general question of the control of gene expression and differentiation.